Why is this study important?
The RADIANCE-HTN TRIO study is important because it first demonstrated the incremental value of ultrasound-based renal denervation (RDN) over sham procedure, for reduction in multiple metrics of SBP control at 2 months, on the backdrop of optimal, fixed-dose antihypertensive therapy. In the 6-month blinded analysis presented at TCT2021, BP reductions were seen in both arms with greater reductions of home SBP (but similar ambulatory SBP) in the RDN arm, achieved with lower doses of additional medications and less use of aldosterone antagonists. Finally, it demonstrated that RDN in this select group of patients was associated with a very acceptable procedural short- and intermediate-term safety profile.
Should I change my practice because of these findings?
While RDN remains investigational in the United States, this study demonstrated that single-tablet, fixed-dose, triple antihypertensive therapy with a calcium channel blocker, ARB, and thiazide diuretic does, in fact, reduce BP in the majority of patients studied, with very high levels of adherence. In those patients who fail to achieve stringent BP goals, despite this approach, ultrasound-based RDN may be an attractive therapeutic option in the future, if FDA-approved.
What question was this study supposed to answer?
This study investigated the value of RDN in patients who had demonstrated tolerance and adherence to multidrug antihypertensive regimens (albeit with suboptimal control of hypertension) and further, were aggressively managed with a fixed-dose 3-drug regimen prior to randomization to RDN vs. sham procedure followed by sequential standardized stepped-care antihypertensive treatment (SSAHT) in both treatment arms after the 2-month study endpoint, from months 2–5.
What did the study show?
RADIANCE-HTN TRIO randomized patients with suboptimally controlled systolic hypertension despite 4 weeks of treatment with fixed-dose, single tablet, triple-antihypertensive therapy to ultrasound-based renal denervation (using the Paradise system by ReCor Medical) versus a sham procedure. It demonstrated that renal denervation reduced daytime ambulatory systolic blood pressure in the intent-to-treat population at 2 months by 8.0 mm Hg vs. 3.0-mm Hg reduction observed in patients treated with the sham procedure. This equated to a median between-group difference of 4.5 mm Hg (P = 0.022). There were also significant between-group reductions in 24-hour ambulatory systolic blood pressure, nighttime ambulatory systolic blood pressure, and office- and home-based systolic blood pressure.
This trial included patients with office blood pressures of >140/90 mm Hg on three or more antihypertensives, including a diuretic. If trial-eligible, patients were then switched to a single, fixed-dose tablet comprised of amlodipine 10 mg (or 5 mg if significant edema occurred), valsartan 160 mg (or olmesartan 40 mg contingent on medication availability), and hydrochlorothiazide 25 mg. If patients still failed to achieve daytime ambulatory blood pressures of <135/85 mm Hg after 4 weeks of treatment, they were then eligible for randomization to renal denervation vs. sham procedure.
During months 2–5, the addition of sequential standardized stepped-care antihypertensive treatment (SSAHT) was recommended if monthly measured home blood pressure was ≥135/85 mm Hg, with the goal of achieving optimal blood pressure control in both groups.
How good was the approach/methodology?
This study was well-conducted at 53 U.S. and European centers and while both the 2-month and 6-month outcomes favored use of RDN on top of optimal multi-drug antihypertensive regimens, it should be noted that of the 989 patients originally enrolled, all but 152 were excluded from the study for a variety of reasons including achievement of adequate BP control on the protocol-mandated fixed-dose regimen.
Furthermore, between months 2 and 5, all patients were subjected to intensive SSAHT with spironolactone 25 mg/d, bisoprolol 10 mg/d, full dose of a centrally acting α2 receptor agonist, and an alpha-1 receptor blocker as needed. Thus, the external applicability of the study suffers somewhat as the patients studied were very aggressively managed (arguably beyond what is often achievable in community practice) and with 71–78% adherence. Moreover, this study cannot be generalized to other RDN systems currently being investigated or other populations of resistant hypertensive patients.
All editors: Jordan Safirstein, MD, FSCAI; Sandeep Nathan, MD, MSc, FSCAI; Kirk N. Garratt, MD, MSc, MSCAI; and David A. Cox, MD, MSCAI
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